On Aug. 13, 2021, Merck announced that the U.S. Food and Drug Administration (FDA) had approved WELIREG, an oral hypoxia-inducible factor-2 alpha (HIF-2a) inhibitor, for the treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors, not requiring immediate surgery. The recommended dose of WELIREG (40 mg tablets) is 120 mg once daily until disease progression or unacceptable toxicity. The approval is based on results from the open-label Study 004 trial (N=61), where the major efficacy endpoint was overall response rate (ORR) in patients with VHL-associated RCC.

WELIREG is the first HIF-2α inhibitor therapy approved in the U.S. As an inhibitor of HIF-2α, WELIREG reduces transcription and expression of HIF-2α target genes associated with cellular proliferation, angiogenesis and tumor growth.

The WELIREG label contains a boxed warning that exposure to WELIREG during pregnancy can cause embryo-fetal harm. Verify pregnancy status prior to the initiation of WELIREG. Advise patients of these risks and the need for effective non-hormonal contraception. WELIREG can render some hormonal contraceptives ineffective. WELIREG can cause severe anemia that can require a blood transfusion. Monitor for anemia before initiation of WELIREG and periodically throughout treatment. WELIREG can cause severe hypoxia that may require discontinuation, supplemental oxygen, or hospitalization. Monitor oxygen saturation before initiation of and periodically throughout treatment with WELIREG.